Drugs Used in the IRS-IV Protocol for Rhabdomyosarcoma
The Intergroup Rhabdomyosarcoma Study-IV (IRS-IV) protocol primarily uses vincristine, dactinomycin (actinomycin D), and cyclophosphamide (VAC) as its core chemotherapy regimen, with alternative arms using ifosfamide and etoposide in certain treatment groups. 1
Primary Chemotherapy Regimens in IRS-IV
VAC Regimen (Main Treatment Arm)
- Vincristine: 1.5 mg/m² weekly
- Dactinomycin (Actinomycin D): Used as part of the multi-agent combination 2
- Cyclophosphamide: Doses ranged from 1.2 g/m² to 2.2 g/m² 3
Alternative Treatment Arms
VAI Regimen:
- Vincristine
- Actinomycin D (dactinomycin)
- Ifosfamide (replacing cyclophosphamide) at 1.8 g/m²/day × 5 days 4
VIE Regimen:
- Vincristine: 1.5 mg/m²/week
- Ifosfamide: 1.8 g/m²/day × 5 days
- Etoposide: 100 mg/m²/day × 5 days 4
Treatment Schedule and Administration
The IRS-IV protocol organized treatment based on risk stratification:
- Most patients were randomized to receive either VAC, VAI, or VIE regimens 1
- Treatment duration was typically 6-12 months depending on response and risk group
- Patients with Group 3 tumors received either conventional radiotherapy or hyperfractionated radiotherapy in addition to chemotherapy 1
Efficacy Outcomes
The three-year failure-free survival rates were comparable between the main treatment arms:
- VAC: 75%
- VAI: 77%
- VIE: 77% 1
Overall three-year survival across all treatment groups was 86%, demonstrating the effectiveness of these regimens 1.
Important Considerations
Toxicity Management
- Myelosuppression occurred in most patients on all regimens
- Toxic deaths occurred in less than 1% of patients 1
- Growth factor support became routine due to high incidence of life-threatening neutropenia and infections 4
Special Populations
- Patients with embryonal tumors particularly benefited from the intensive three-drug chemotherapy in IRS-IV (3-year FFS: 83%) 1
- Younger patients with Group 1 paratesticular embryonal tumors and patients with Group 1/2 orbit or eyelid tumors showed excellent outcomes with VA chemotherapy alone 1
Evolution from Previous Protocols
The IRS-IV protocol built upon findings from IRS-III, showing improved outcomes with the three-drug regimen for many patient subgroups, particularly those with embryonal histology 1.
Conclusion
The IRS-IV protocol demonstrated that VAC, VAI, and VIE regimens were equally effective for patients with local or regional rhabdomyosarcoma. The core drugs used in the IRS-IV protocol were vincristine, dactinomycin, and cyclophosphamide, with ifosfamide and etoposide serving as important alternatives in specific treatment arms.